A pentacosapeptide (CKS-25) homologous to retroviral envelope proteins possesses a transforming growth factor-beta activity.
CKS-17, a synthetic heptadecapeptide homologous to a conserved domain in retroviral envelope protein p15E, mimics the immunosuppressive properties of p15E in vitro and in vivo, but the mechanisms are not understood. Here we report that a synthetic pentacosapeptide designated CKS-25, a longer version of CKS-17 that contains a functional transforming growth factor-beta3 (TGF-beta3) active-site motif (RXXD), inhibits 125I-labeled TGF-beta1 (125I-TGF-beta1) binding to cell-surface TGF-beta receptors in cultured epithelial cells. Multiple conjugation of CKS-25 to bovine serum albumin and carbonic anhydrase enhances the 125I-TGF-beta1 binding inhibitory activity and confers a partial TGF-beta agonist activity (growth inhibition but not transcriptional activation). Since TGF-beta is a potent immunosuppressive factor, these results suggest that the immunosuppressive properties of CKS-17-bovine serum albumin conjugate and p15E are mediated at least in part by their TGF-beta agonist activities.
Huang
S S
SS
Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Huang
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017124:Conserved Sequence; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000166:cytology; D008907:Mink; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011485:Protein Binding / Q000187:drug effects; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000819:agonists*; D014759:Viral Envelope Proteins / Q000235:genetics
C110956:CKS 25; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D018125:Receptors, Transforming Growth Factor beta; D015682:Retroviridae Proteins, Oncogenic; D016212:Transforming Growth Factor beta; D014759:Viral Envelope Proteins